AUTHOR=Miao Lingrui , Zhou Run , Zhang Longfei , Feng Linlu , Wang Yiao , Song Pan , Lv Dong , Shen Tai-Min 

TITLE=Unraveling the dual roles of tumor-infiltrating antibodies in solid tumors: friend or foe in the tumor microenvironment?

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1671839

DOI=10.3389/fimmu.2025.1671839

ISSN=1664-3224

ABSTRACT=Within the tumor microenvironment (TME) of solid malignancies, tumor-infiltrating antibodies, have been identified as significant modulators of tumor progression and immune response. Tumor-infiltrating antibodies predominantly secreted by plasma cells but also including a small proportion of cancer-derived antibodies. This review aims to elucidate the multifaceted roles of tumor-infiltrating antibodies in the immunology of solid tumors, focusing on their dualistic nature within the TME. This review outlines the mechanisms of B cell activation, antibody class switching, plasma cell differentiation and antibody production, with a focus on their contributions to tumor immunity in solid cancers. Additionally, we discuss the emerging potential of tumor-infiltrating antibodies as both therapeutic targets and diagnostic biomarkers, offering insights that may inform future strategies in cancer treatment. Collectively, antibody functions are shaped by their isotypes: IgG is often associated with improved prognosis in various solid tumors. IgG1 and IgG3 generally mediate anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), while IgG4 may impair immune effector functions and associate with immune tolerance. IgM, as an early humoral responder, enhances tumor surveillance through complement dependent cytoxicity (CDC), phagocytosis, and apoptosis induction. IgA predominantly promotes tumor progression through immune suppression. IgE exhibits context-dependent pro- and anti-tumor activities, though current evidence is limited, whereas the function of IgD remains largely unknown. Additionally, tumor-derived IgG promotes tumor growth, metastasis, and immune evasion. These findings may open new avenues of research to develop targeted therapies that modulate tumor-infiltrating antibodies, potentially improving the efficacy and safety profiles of current immunotherapeutic approaches. Overall, this review focuses on tumor-infiltrating antibodies in solid tumors and does not encompass hematological malignancies, aiming to provide a more precise understanding of antibody-mediated regulation within the solid tumor microenvironment.